Scrofuloderma

A 60‐year‐old woman presented to the Dermatology Department of Dokuz Eylül University Faculty of Medicine with complaints of hardened reddenings and inflammatory drainage on her right armpit, groin, and hips. These lesions appeared 2 months after a cholecystectomy operation, which had been performed 4 years ago, and showed unilateral progression. The patient had been treated unnecessarily with prednisolone (5 mg every other day) for 7 years because of arthralgia.

The biopsy result of the hypopigmented patch showed an essentially normal looking epidermis and dermis; there was no melanin incontinence. The verrucous patch showed hyperkeratosis, psoriasiform hyperplasia of the epidermis with regular alternation of parakeratotic areas with hypergranulosis and orthokeratosis with a reduction in the granular layer.

Discussion
Nevus depigmentosus (ND) is a congenital pigmentary disorder characterized by hypopigmented patches, which could present in three different ways: (i) isolated (circular or rectangular), (ii) segmental, and (iii) systematized. The last variant usually follows Blaschko's lines. 1 There is no known pattern of inheritance 2 or sex predominance. The clinical features are constant and permanent throughout life and it is rarely associated with other congenital abnormalities, although a case of ND with mental retardation and seizures has been reported. 3 ND is believed to result from impaired transfer of melanosomes from melanocytes to keratinocytes 4 and the number of melanocytes are reported to be either normal or slightly reduced. 2 The differential diagnoses of ND include hypomelanosis of Ito (incontinentia pigmenti achromians) in which there are hypopigmented bands and whorls occurring along Blaschko's lines, which tend to occur within the first year of life, with a variability in clinical presentation. 5 A significant number of patients with this disorder have other associated congenital abnormalities. 6 In view of the similarity in clinical presentation of hypomelanosis of Ito and ND, some authors have suggested that both should be referred to as hypomelanosis of Ito with or without systemic abnormalities, respectively 7 as the case may be.
Another differential diagnosis of ND is the fourth stage of incontinentia pigmenti with hypopigmented atrophic lesions found mainly on the lower limbs. 8 In most cases there is a previous history of the vesicular, Figure 1 Hypopigmented whorls, bands, and streaks on both front (a) and back (b) of patient. Note also the one-sided distribution of the ILVEN (affecting the neck, left parasternal area, and dorsal surface of the hand) verrucous, and hyperpigmented stages of incontinentia pigmenti and a positive family history. Histology of the hypopigmented lesions in such patients shows an absence of hair and sweat glands. 9 Linear epidermal nevi frequently follow Blaschko's lines and there have been attempts to classify them into various clinical types. The presentation of pruritus, recurrent inflammation, and localization to the left side of the body in this patient suggests inflammatory linear epidermal verrucous nevi (ILVEN) which describes an inflamed variety of the epidermal nevus. [10][11][12] The fragility of some of the lesions and the sloughed-off areas in some parts are suggestive of the epidermolytic hyperkeratosis variant, 7 although it is generally agreed that the presence of epidermolytic hyperkeratosis in a nevus is determined histologically. The histological appearances in our patient show a slight variation from the normal description of ILVEN in that the parakeratotic areas are associated with hypergranulosis, while the orthokeratotic areas show a reduction in the thickness of the granular layers. This suggests that the various clinical entities in linear epidermal nevi may occur as a spectrum and not as distinct variants in themselves. Hypopigmentation surrounding ILVEN has been previously documented; 13 the hypopigmented lesions found in association with the verrucous lesions in our patient were areas where the verrucous lesions had sloughed off.
The occurrence of different clinical types of epidermal nevi in the same individual does exist, but we find the association of linear epidermal nevi and nevus depigmentosus in the same patient unusual. In addition, the histological appearances of the lesions in this patient are definitely uncommon. This combination of problems may suggest an underlying gene disorder, but unfortunately we do not have facilities for chromosomal studies to even start to pursue the basis of this patient's problem. Two weeks later the patient was seen in the dermatology clinic. She complained of unabated pruritus and extensive new lesions. Physical examination revealed a moderately obese woman with normal vital signs. Firm gray plaques with an irregular contour were present on the left hand. The buttocks (Fig. 2) and extensor aspects of her upper arms were strikingly indurated and had a blue-gray discoloration. Violaceous, indurated oval patches were noted on the medial aspect of both knees. Finally, a slate-colored, irregularly outlined plaque on the heel of the right foot was present. Complete blood count revealed: WBC, 16.5; differential, 8 neutrophils, 9 lymphocytes, 81 eosinophils, and 2 monocytes. The differential was repeated and confirmed. The platelet count was 568,000/mm 3 .

References
A skin biopsy from the patient's left upper arm revealed a superficial and deep perivascular dermatitis. In addition, the dermis had a dense inflammatory infiltrate consisting of numerous interstitial eosinophils, many of which were degranulated. Collagen bundles coated with eosinophilic granules characteristic of flame figures were abundant (Fig. 3). The changes were consistent with eosinophilic cellulitis. Chest X-ray revealed no evidence of infiltrates. A course of oral corticosteroids was prescribed. One week later, the lesions were substantially less indurated, but otherwise similar in appearance. Complete blood count revealed: WBC, 9.9; differential: 21 neutrophils, 19 lymphocytes, 1 basophil, 51 eosinophils, and 8 monocytes. The platelet count was 408,000/mm 3 . Hematologic consultation was arranged for bone marrow biopsy and examination. Unfortunately, the patient did not return for subsequent appointments.

Discussion
Wells' syndrome is an idiopathic inflammatory dermatosis first described by Wells in 1971 1 as ''recurrent granulomatous dermatitis with eosinophilia.'' Spigel and Winkelmann 2 named the condition, ''Wells' syndrome'' in 1979. Wells and Smith 3 proposed the ''simpler title'' of eosinophilic cellulitis while describing eight additional cases. The acute or cellulitic stage lasts several days, and is characterized clinically by erythematous, edematous plaques which may form blisters. The lesions are often accompanied by an intense itching or burning sensation. The predilected anatomic sites are the extremities and trunk. Symptoms, such as arthralgia, malaise, and fever, are occasionally present. The differential diagnosis at this stage includes urticaria, acute bacterial cellulitis, or erysipelas. Some have noted a resemblance to erythema chronicum migrans 4 and granuloma annulare. 3,5 Allergic contact dermatitis has also been simulated. [6][7][8] During the subacute or infiltrative stage, the redness and edema gradually subside and the lesions become indurated, obtain a grayish coloration, and may resemble morphea. This stage lasts several weeks to months, after which there is gradual regression; however, relapse is common with exacerbations and remissions of variable duration.
The characteristic histologic features in the acute stage are dermal edema and diffuse infiltration with eosinophils. Few conditions are characterized by such large numbers of eosinophils in the reticular dermis. 9 The subacute stage is characterized by scattered ''flame figures,'' which consist of a central core of collagen bundles coated with eosinophilic debris, phagocytic histiocytes, and giant cells. The eosinophilic material contains major basic protein (MBP), an arginine-and lysine-rich protein which comprises more than 50% of the core of the major granules of the eosinophil. 10 MBP has been localized to flame figures by indirect immunofluorescence, and has been implicated in their formation by binding to and altering collagen. 5 The Figure 1 Left hand reveals a bulla and several vesicles at the site of the centipede bite recurrent nonscarring nature of Wells' syndrome suggests that flame figures do not result from the destruction of connective tissue by MBP. This has been confirmed by electron microscopy. 11 The presence of flame figures is the most salient histopathologic finding of Wells' syndrome, but they may be seen in various unrelated disorders, including follicular mucinosis, bullous pemphigoid, herpes gestationis, eczema, urticaria, arthropod bites, and dermatophyte infections. 3,4 This has led some to question the existence of Wells' syndrome as a separate entity. 4 Others assert that the diagnosis should not be based on the pathologic findings alone, but should be limited to those patients who also Blue-gray discoloration and induration of the buttocks as well as the proximal thighs is seen. These changes became apparent several weeks after the initial blistering reaction of the hands Our case is unusual in terms of the striking peripheral eosinophilia and the triggering event. Although eosinophilia is not necessary for the diagnosis, it is seen in the majority of patients and is the most constant blood abnormality. In a summary of 24 patients, eosinophilia ranged from 2 to 48%. 6 Nine of the 24 patients had eosinophils greater than or equal to 30% of the white blood cells, while the highest percentage reported was 48%. Our patient' eosinophils ranged from 31 to 81%, and this is the highest range reported to date.
Although its etiology and pathogenesis are unknown, Wells' syndrome, like erythema multiforme, erythema nodosum, and leukocytoclastic vasculitis, represents a reaction pattern to a number of different stimuli. Reported triggers of Wells' syndrome include fungal 3 and parasitic infections, 15 drug eruptions, 1-3 underlying hematologic disorders, 1,5,7,9 and insect bites. [2][3][4][5]7,13,14,16,17 The theory that insect bites trigger some cases was first proposed by Wells and Smith. 3 Insect bites are frequently considered when the lesions first appear. In some cases, the patient has specific knowledge of a bite and may bring the insect to the physician for examination. 4 Specific reports have attributed cases of Wells' syndrome to mosquitos, 3 spiders, 4,16,17 ticks, 4 fleas, 4,5 ''buffalo gnats,'' 5 and mites. 13 Two patients described being stung by a small bee or wasp. 4,14 The present report is the first to describe a case triggered by a centipede bite.
Centipedes, nocturnal predators of insects and other small animals, are commonly found in the USA, India, and Australia. These 3-250-mm-long arthropods have one pair of legs per body segment, which aids in distinguishing them from other arthropods. Although they most often hide under stones, tree bark, and in holes, they commonly set up residence in households. Specifically, Scutigera coleoptrata is found throughout most of eastern North America. The bite of a centipede is seldom fatal to humans, often causing only local skin reaction. Several patients have experienced burning pain, redness, and edema, sometimes leading to an erysipelas-like state, 18,19 while others have reported more severe reactions, such as myonecrosis. 20 We describe the first report of eosinophilic cellulitis occurring in association with a centipede bite. The variation of responses described is not species specific, and is most likely secondary to patients' individual reactions to the bite.
Treatment of Wells' syndrome with systemic steroids leads to resolution in most patients, but this may take several weeks to occur. Dapsone 15,21 has been used successfully on rare occasions. Griseofulvin has also had limited success. 3,21,22 Several cases have demonstrated spontaneous resolution. Response to treatment in our patient could not be evaluated.
In summary, the present case, precipitated by a centipede bite, displays the characteristic clinical features, course, and histologic findings typical of Wells' syndrome. This entity, although rare, should be considered in a patient with an atypical ''cellulitis'' resulting from an insect bite that does not resolve with oral antibiotics. In such cases, eosinophilic cellulitis can be readily confirmed by skin biopsy and remedied with steroid therapy. observable fistula located distally on the regio abdominalis lateralis dextra and another scar in a lateral position were observed. There were also abscesses, fistulas, and scars on the regio inguinalis and regio glutealis dextra (Fig. 1). Systemic examination was normal.
A tuberculin test showed erythema (9 cm) and induration in 72 h. Bacterial, mycotic, and tuberculous cultures of the vacuum and smear samples from the lesions and urine showed no reproduction.
A histopathologic examination of the biopsy material revealed nonspecific slight acanthosis, perivascular mononuclear cellular infiltration in the superficial dermis, and a dense mononuclear cellular infiltration in the subcutis.
The deoxyribonucleic acid obtained from the pus liquid by the phenol-chloroform method for the detection of mycobacterium tuberculosis with polymerase chain reaction was amplified using primers specific to microorganisms in the mycobacterium tuberculosis complex and also specific to the IS 6110 region. At the end of the molecular analysis, a product of amplification of 123 bp specific to mycobacterium tuberculosis was found.
The erythrocyte sedimentation rate was 92 mm/h. All other laboratory values were normal, including biochemical analysis, anti-human immunodeficiency virus, venereal disease research laboratory test, and rheumatoid factor. X-Ray and high-resolution computerized tomography examination of the chest, rectosigmoidoscopy, esophagus, stomach, duodenum, and small intestine passage X-ray examinations, and vaginal smear inspections, performed to investigate other organ tuberculosis, did not show any pathologic finding. The arthralgic complaints of the patient were assessed as degenerative arthrosis by considering the bone-joint X-ray examinations.
Isoniazid 300 mg/day and rifampicin 600 mg/day were given to the patient and, since the sixth week of administration, no drainage from fistulas was observed. At the end of 9 months of treatment, the lesions improved, with scar formation, and no new lesions were observed (Fig. 2). The improvement has continued in the 4 months following the completion of therapy.

Discussion
Scrofuloderma, also called tuberculosis cutis colliquativa, is a subacute form of skin tuberculosis, which is characterized by subcutaneously located, cold abscess formation and secondary changes of the overlying skin. It can be caused by direct invasion of the bacilli to the skin from the International Journal of Dermatology 1998, 37, 600-616 © 1998 Blackwell Science Ltd lesions of patients with tuberculosis of the lymph nodes, epididymis, bones, and joints, as well as by exogenous introduction of the bacilli by trauma or injection. 1 Scrofuloderma often originates in children from the neck lymph nodes during the primary tuberculosis complex. Despite this, a child case of isolated liver tuberculosis and associated scrofuloderma development of the overlying Figure 1 Clinical picture before treatment skin has been reported . 2 The elderly often have more than one lesion, depending on the hematogenous invasion, and these lesions can be seen on the trunk, inguinal, and gluteal regions and on the tongue, in addition to the neck region. 3 Occasionally, scrofuloderma can occur by direct exogenous inoculation of the bacilli to the skin. Scrofuloderma evolving over the lacrimal duct skin by exogenous inoculation and cases of atypical mycobacterium infection developing after blepharoplasty surgery have been reported. 4,5 In our patient, the initial complaints had begun following a cholecystectomy operation and showed unilateral progression. Lung and other organ system tuberculosis was investigated and no finding was detected. The administration of low dose corticosteroids for a long time facilitated the progression of scrofuloderma in this case.
The sensitivity of tuberculous cultures from skin lesions is often low, and reproduction may not be established every time. 1,6,7 In recent years, it has been reported that mycobacterial deoxyribonucleic acid analysis by polymerase chain reaction is the fastest and most important method of diagnosis. 8 The advantages of this method are that it does not necessarily require viable cells and the Clinical picture after treatment rapid elucidation of the results. 6 In developing countries, where tuberculosis can appear frequently and the empirical administration of antituberculous drugs is performed due to the difficulties in establishing the diagnosis by culture, the practice of polymerase chain reaction is primarily of great importance. 9 Although the culture taken from the abscess material on the gluteal region in our case showed no reproduction, deoxyribonucleic acid amplification products unique to mycobacterium tuberculosis were established by polymerase chain reaction, and this played an important role in planning the therapy of the case within a short time. There were no urticarial lesions, and the oral mucosa and scalp were spared.
A biopsy specimen of lesional skin from the left thigh revealed epidermal detachment at the dermal-epidermal junction with prominent festooning of dermal papillae. A dense, perivascular lymphohistiocytic infiltrate was present in the underlying dermis (Fig. 3). Welldefined neutrophilic papillary microabscesses were not identified, nor were eosinophils. Direct immunofluorescence (DIF) staining revealed linear deposition of immunoglobulin A (IgA) at the dermal-epidermal junction (Fig. 4). Indirect immunofluorescence studies of the serum were negative for circulating pemphigus and pemphigoid antibodies. On the basis of these findings, a diagnosis of linear IgA bullous dermatosis was made.
Despite discontinuation of captopril, the patient continued to develop new blisters. Treatment with dapsone was initiated at a dose of 25 mg t.i.d. Because of continued blister formation, the dose was increased to 50 mg t.i.d. and prednisone was added to the regimen. The latter was tapered over a period of 3 months. For the past year, dapsone has been administered at a dosage of 100 mg b.i.d., and the patient has experienced only occasional blister formation. along the basement membrane zone. Most characteristically, tense vesicles are arranged in herpetiform, sausagelike, rosette-like, or arciform patterns on erythematous or normal-appearing skin. Histologic examination reveals subepidermal bullae and papillary microabscesses con- Although LABD is usually idiopathic, drug-induced disease has been described. While vancomycin is the agent most commonly implicated, 1-5 other agents include phenytoin, 1 somatostatin, 1 amiodarone, 6 lithium, 7 cefamandole, 8 and diclophenac. 9 Captopril, an angiotensin-II-converting enzyme inhibitor, is a widely used antihypertensive agent that has been associated with a wide variety of cutaneous reactions, including angioedema, 10,11 urticaria, 11 lichenoid eruptions, 12 and pityriasis rosea. 13 While its role as an etiologic factor in pemphigus is well established, 14,15 its role as a causative agent in other bullous dermatoses has only rarely been repoted . [16][17][18][19] It has been implicated in two prior reports of LABD. 1,20 Drug-induced LABD is characterized by the spontaneous remission of the blisters after the removal of the offending drug. Idiopathic LABD, in contrast, tends to have a protracted course, frequently requiring treatment with dapsone and occasionally systemic corticosteroids. 3 To date, all reported drug-induced LABD cases have demonstrated the resolution of blisters within days to several weeks of discontinuation of the drug ( cessation of the implicated drug. In addition, she required treatment with dapsone and corticosteroids for complete control of the blistering process. This suggests that the drug may have induced the expression of a pre-existing bullous dermatosis. Reports that have unequivocally established a drug as an etiologic factor by virtue of its reintroduction as a therapeutic agent are few in number. 7,9 In many cases, multiple drugs were administered simultaneously and one specific agent could, at best, be labeled the most likely culprit. 2 Although, in the absence of a drug rechallenge, we cannot prove with certainty that captopril induced the eruption in our patient, the temporal relation of her symptoms to the administration of this drug is highly suggestive of a drug etiology.

Linear immunoglobulin A (IgA) bullous dermatosis (LABD) is a subepidermal vesicobullous eruption occurring in adults and characterized by a linear pattern of IgA deposition
The clinical appearance of LABD is morphologically variable. LABD was originally considered to be a variant of DH, with which it may be confused. Its clinical features may also resemble BP. The diagnosis in the present case was initially suggested by the characteristic arciform arrangement of blisters in several areas.
The histopathologic features in LABD are equally variable. Most typically, histologic examination reveals a subepidermal bulla and papillary microabscesses containing numerous inflammatory cells-predominantly neutrophils and occasionally eosinophils; however, the pathologic features often suggest the diagnosis of DH or BP. Rarely, erythema multiforme-or toxic epidermal necrolysis-like clinical or pathologic changes are identified. 8,20 The inconstant clinical and histopathologic manifestations of LABD may indicate that several pathogenic  mechanisms are operative in this disease, which, in turn, may affect therapeutic decision making. This may explain, in part, why some cases of LABD are not responsive to dapsone, the drug of choice. Although the clinical presentation of our patient was characteristic, the pathologic findings were less typical. Of interest is the dense perivascular lymphohistiocytic dermal infiltrate. To the best of our knowledge, this feature, in the absence of infiltrating polymorphonuclear leukocytes, has not been previously Histologic examination of a skin biopsy specimen revealed a subepidermal blister containing neutrophils and eosinophils, and an infiltrate of lymphocytes with eosinophils and neutrophils in the superficial dermis. Direct immunofluorescence of perilesional skin showed a linear band of immunoglobulin G (IgG) and C3 at the dermo-epidermal junction. Indirect immunofluorescence on 1 mol/L sodium chloride-split normal skin showed IgG deposits on the dermal side of the blister. Western immunoblot analysis of the reactivity of the patient's serum on epidermal and dermal extracts revealed that autoantibodies were bound to the 290-kDa antigen in the dermal extract (Fig. 2). No reactivity was observed in the epidermal extract.
The boy was treated with prednisolone (1.3 mg/kg body weight per day) which inhibited new blistering. Since a reduction of the dose of prednisolone to 1.1 mg/kg body weight per day induced new blistering,dapsone (1.6 mg/kg body weight per day) and prednisolone (1.1 mg/kg body weight per day) were given in combination, leading to improvement. A further decrease in the dose of prednisolone to 0.9 mg/kg body weight per day resulted in new bulla formation, and the prednisolone was replaced by betamethasone. The disease activity then markedly subsided and the bullae healed with the formation of milia.

Discussion
Epidermolysis bullosa acquisita (EBA) is an acquired bullous disease which is characterized by immunoglobulin G (IgG) autoantibodies that react with type VII collagen in the anchoring fibrils, leading to the formation of bullae at the dermo-epidermal junction. 1 EBA is a rare disease in childhood: we found only 18 cases in the literature. [2][3][4][5][6][7][8][9][10][11][12] In both children and adults, there are two main clinical phenotypes of EBA. 13 The classic, non-inflammatory, mechanobullous type involves skin fragility, blisters at sites of trauma, and healing with scarring and milia. The inflammatory type resembles most chronic bullous disease, including bullous pemphigoid, cicatrical pemphigoid, and linear IgA bullous disease. During the course of his disease, our patient presented both cutaneous phenotypes of EBA. Although mucosal (oral in particular) involvement is frequent and severe, occurring in 13 of 16 cases in which EBA was described, our patient did not show this sign. Patients of various races have been reported: eight white, five black, one from Iran, and one from the Philippines. Our patient seems to be the first reported Japanese case.
Indirect immunofluorescence on split skin is helpful in differentiating between EBA and other types of autoimmune bullous diseases, but cannot replace immunoblotting, because, in rare cases, fluorescent binding may also occur on the dermal side in bullous pemphigoid. 14 The combination of dapsone and prednisolone appears to be the most effective treatment for pediatric EBA, and the prognosis in children seems better than in adults.  small nodule on the scalp which discharged cheesy material and was suggestive of Tamil Nadu India calcinosis cutis. The right index finger showed a broad terminal phalanx. Gynecologic examination revealed a small infantile uterus. The patient had normal dentition.

Cases 2 and 3
Two brothers, aged 6 and 3 years, who were brought to the clinic for screening, also revealed similar skeletal and cutaneous changes, but with less intense pigmentation. Both had normal development of the genitalia. Case 4 After 4 years, another girl of 15 years of age was referred to us with complaints of inability to walk due to pain in the feet. The patient was born to second-degree consanguineous parents and showed the same clinical features as those of Case 1, except for short stature (height, 138 cm) and a broad terminal phalanx on the left middle finger. This female patient also had an infantile uterus.
All four patients were subjected to routine investigations, which were found to be within normal limits. Examination of the hair under potassium hydroxide mount did not reveal any abnormality.
Skeletal surveys were performed for all patients. In Case 1, an X-ray of the skullanteroposterior (AP) and lateral view (Fig. 2) revealed frontal bossing of the cranial vault. Coronal, lambdoid, and sagittal sutures were widened, measuring 5, 5, and 7 mm, respectively. The cranial vault had a ground glass appearance and did not show outer and inner table differentiation. The metopic and mendosal sutures were seen. The sutures were seen as straight lines instead of serrated interdigitations. The occipital area showed only a sea of membranes with islands of ossified bones (Wormian bones). Platybasia was seen. The mandible was hypoplastic. A chest X-ray revealed a narrow chest cavity with normal clavicles. An X-ray of the spine was normal. An X-ray of the pelvis showed increased acetabular angles, collapsed head of femur, and reduced shaft neck angle. An X-ray of the hand showed popcorn calcification in the soft tissues. There was hypoplasia of the distal part of the terminal phalanx of the left index finger. An X-ray of the foot also showed similar soft tissue calcification of the left big and little toes.
Skeletal surveys of the two other siblings revealed Wormian bones and widened suture lines, but were otherwise normal. A skeletal survey of the fourth case also reflected the same changes as in Case 1, except that hypoplasia of the terminal phalanx of the left middle finger was observed.
Histopathology of the scalp nodule of Case 1 and of the keratotic papules of Cases 1 and 4 ( Fig. 3) revealed calcified deposits in the mid and lower dermis which stained positive with Von Kossa.

Discussion
The first three patients from the same family were seen in 1992, and the fourth patient was seen 4 years later. The combination of poikilodermatous skin lesions with identical radiologic features led us to suspect one of the premature aging syndromes. Familial mandibuloacral dysplasia (MAD) is a very rare syndrome, first described by Danks et al. 1 in 1974. Over the last two decades, very few cases of this syndrome have been reported in the world literature. [2][3][4][5] The condition appears to be inherited as an autosomal recessive trait and seems to be more common in Italy, according to Tenconi et al. 5 An autosomal recessive mode of inheritance was first suspected by Zina et al. 2 in 1981, because two sets of third cousins with MAD hailed from a small mountain village. Tenconi et al. 5 confirmed the mode of inheritance in all their patients. In our series also, the patients were born to second-degree consanguineous parents.
The features of MAD syndrome usually start between 3 and 5 years of age. 5 Schrander et al. 3 described a patient who developed changes at 2 years of age. All of our patients had normal development until 3-5 years of age, by which time they had developed poikilodermatous skin lesions. Although the skin lesions started later, all had defects in the skull bone at birth.  All four patients in our series showed these features, with the exception of dysplastic clavicle and loss of lower teeth. Interestingly, both of the female patients developed soft tissue calcification, which was confirmed by histopathology of the nodular and keratotic papules, and by radiology which revealed popcorn calcification of the extremities. They also had an infantile uterus. Calcinosis cutis has been less frequently reported with MAD syndrome, according to Tenconi et al. 5 Infantile uterus has not been reported.  MAD syndrome may be mistaken for hereditary sclerosing poikiloderma. Both conditions show poikilodermatous skin changes, but the presence of keratotic papules and skeletal changes differentiates the two entities. Fryburg and Sidhu 4 described two siblings of MAD syndrome in whom the diagnosis of hereditary sclerosing poikiloderma was made initially but, on re-evaluation as adults, the clinical features were perceived to be compatible with MAD syndrome. This syndrome may also be mistaken for any of the premature aging syndromes, such as Werner's syndrome, because of the predominant feature of premature aging, but only MAD syndrome is associated with Wormian bones in the skull.